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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Review Article

The Metabolism and Pharmacokinetics of Rhein and Aurantio-Obtusin

Author(s): Shun-Li Xiao, Liang-Jun Guan, Ren-Feng Jiang, Xiang-Gen Wang, Xing Li and Wei Cai*

Volume 21, Issue 12, 2020

Page: [960 - 968] Pages: 9

DOI: 10.2174/1389200221666200719002128

Price: $65

Abstract

Background: Anthraquinones, rhein and aurantio-obtusin were isolated from the herb Duhaldea nervosa for the first time by our group, which were also found in plants that belong to the plant family Compositae. Anthraquinone compounds have a range of pharmacological activities such as anti-inflammatory, anti-cancer, antioxidation, anti-diabetes, etc. and can be used as a laxative, for liver protection, treatment of chronic renal failure, etc. However, in recent years, anthraquinones have been reported to be cytotoxic to the liver and kidneys. Therefore, it is very important to study the pharmacokinetics and metabolism of rhein and aurantio-obtusin, which are common ingredients in many traditional Chinese medicines (TCM). According to our research, the pharmacokinetics and metabolism of rhein and aurantio-obtusin are comprehensively summarized in the paper for the first time.

Objective: The study provides comprehensive information on pharmacokinetics and metabolism of rhein and aurantio- obtusin in different Species; meanwhile, the aim of this review is also to provide a reference for a reasonable application of TCM enriched with these two ingredients.

Methods: The metabolism and pharmacokinetics of rhein and aurantio-obtusin were searched by the Web of Science, PubMed, Google scholar and some Chinese literature databases.

Results: Rhein and aurantio-obtusin exist mainly in the form of metabolites in the body. Rhein and aurantio-obtusin and its metabolites might be responsible for pharmacological effects in the body. Therefore, the significance of studying the in vivo metabolites of rhein and aurantio-obtusin is not only essential to clarify their pharmacological mechanism, but also to find new active compound ingredients. The metabolism of rhein is different in different species, so the toxicity effects of rhein may also be different after oral administration in different species; however, the metabolic profiles of aurantio-obtusin in the liver microsomes of different species are similar.

Conclusion: This paper not only provides detail regarding the pharmacokinetics of rhein and aurantio-obtusin, but it is anticipated that it will also facilitate further study on the metabolism of rhein and aurantio-obtusin.

Keywords: Duhaldea nervosa, rhein, aurantio-obtusin, anthraquinones, pharmacokinetics, metabolism.

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[1]
Xiao, C.W. Explore Secret of Dong Medicine; YueluPress: ChangSha, 2004.
[2]
Xiao, C.W. Textual research of dong medicineanda famous doctor for treating traumatic injury. Chin.J. Ethnomed. Ethnopharm., 1997, 5, 41-42.
[3]
Long, S. Clinical experience of “maoshoucai” for treating traumatic injury. Chin. J. Ethnomed. Ethnopharm., 2004, 12, 231-232.
[4]
Yan, L.; Huang, Y.; Fu, J.J.; Qin, J.J.; Zeng, Q.; Zhu, Y.; Yan, S.K.; Zhang, W.D.; Jin, H.Z. Three new phenylpropanoids from Inulanervosa Wall. Helv. Chim. Acta, 2010, 93, 1418-1421.
[http://dx.doi.org/10.1002/hlca.200900432]
[5]
Yan, L. Studies on the constituents from Inula nervosa Wall. ,Master thesis, Shanghai Jiao Tong University: Shanghai, 2010.
[6]
Yan, L.; Jin, H.Z.; Nie, L.Y.; Qin, J.J.; Fu, J.J.; Zhang, W.D. Chemical constituents from Inula nervosa Wall. Nat.Prot.Res.Dev., 2011, 2, 258-261.
[http://dx.doi.org/ 10.1093/mp/ssq070]
[7]
Yan, L.; Cheng, X.R.; Zeng, Q.; Qin, J.J.; Zhang, W.D.; Jin, H.Z. Phytane and neoclerodane diterpenes from the aerial parts of Inula nervosa Wall. Biochem. Syst. Ecol., 2011, 39(4-6), 700-703.
[http://dx.doi.org/10.1016/j.bse.2011.06.001]
[8]
Sheng, X.; Wang, M.; Lu, M.; Xi, B.; Sheng, H.; Zang, Y.Q. Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice. Am. J. Physiol. Endocrinol. Metab., 2011, 300(5), E886-E893.
[http://dx.doi.org/10.1152/ajpendo.00332.2010] [PMID: 21364120]
[9]
Peng, S.N.; Zeng, H.H.; Fu, A.X.; Chen, X.W.; Zhu, Q.X. Effects of rhein on intestinal epithelial tight junction in IgA nephropathy. World J. Gastroenterol., 2013, 19(26), 4137-4145.
[http://dx.doi.org/10.3748/wjg.v19.i26.4137] [PMID: 23864776]
[10]
Su, J.; Yin, L.P.; Zhang, X.; Li, B.B.; Liu, L.; Li, H. Chronic allograft nephropathy in rats is improved by the intervention of rhein. Transplant. Proc., 2013, 45(6), 2546-2552.
[http://dx.doi.org/10.1016/j.transproceed.2013.03.030] [PMID: 23953579]
[11]
Moldovan, F.; Pelletier, J.P.; Jolicoeur, F.C.; Cloutier, J.M.; Martel-Pelletier, J. Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthritis Cartilage, 2000, 8(3), 186-196.
[http://dx.doi.org/10.1053/joca.1999.0289] [PMID: 10806046]
[12]
Tamura, T.; Kosaka, N.; Ishiwa, J.; Sato, T.; Nagase, H.; Ito, A. Rhein, an active metabolite of diacerein, down-regulates the production of pro-matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of tissue inhibitor of metalloproteinase-1 in cultured rabbit articular chondrocytes. Osteoarthritis Cartilage, 2001, 9(3), 257-263.
[http://dx.doi.org/10.1053/joca.2000.0383] [PMID: 11300749]
[13]
Cong, X.D.; Ding, M.J.; Dai, D.Z.; Wu, Y.; Zhang, Y.; Dai, Y. ER stress, p66shc, and p-Akt/Akt mediate adjuvant-induced inflammation, which is blunted by argirein, a supermolecule and rhein in rats. Inflammation, 2012, 35(3), 1031-1040.
[http://dx.doi.org/10.1007/s10753-011-9407-4] [PMID: 22095404]
[14]
Fernand, V.E.; Losso, J.N.; Truax, R.E.; Villar, E.E.; Bwambok, D.K.; Fakayode, S.O.; Lowry, M.; Warner, I.M. Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro. Chem. Biol. Interact., 2011, 192(3), 220-232.
[http://dx.doi.org/10.1016/j.cbi.2011.03.013] [PMID: 21457705]
[15]
Lin, M.L.; Chung, J.G.; Lu, Y.C.; Yang, C.Y.; Chen, S.S. Rhein inhibits invasion and migration of human nasopharyngeal carcinoma cells in vitro by down-regulation of matrix metalloproteinases-9 and vascular endothelial growth factor. Oral Oncol., 2009, 45(6), 531-537.
[http://dx.doi.org/10.1016/j.oraloncology.2008.07.012] [PMID: 18804415]
[16]
Chung, J.G.; Tsou, M.F.; Wang, H.H.; Lo, H.H.; Hsieh, S.E.; Yen, Y.S.; Wu, L.T.; Chang, S.H.; Ho, C.C.; Hung, C.F. Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients. J. Appl. Toxicol., 1998, 18(2), 117-123.
[http://dx.doi.org/10.1002/(SICI)1099-1263(199803/04)18:2<117: AID-JAT486>3.0.CO;2-D] [PMID: 9570694]
[17]
Yu, L.; Xiang, H.; Fan, J.; Wang, D.; Yang, F.; Guo, N.; Jin, Q.; Deng, X. Global transcriptional response of Staphylococcus aureus to rhein, a natural plant product. J. Biotechnol., 2008, 135(3), 304-308.
[http://dx.doi.org/10.1016/j.jbiotec.2008.04.010] [PMID: 18514345]
[18]
Sheng, X.; Zhu, X.; Zhang, Y.; Cui, G.; Peng, L.; Lu, X.; Zang, Y.Q. Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int. J. Biol. Sci., 2012, 8(10), 1375-1384.
[http://dx.doi.org/10.7150/ijbs.4575] [PMID: 23139635]
[19]
Raimondi, F.; Santoro, P.; Maiuri, L.; Londei, M.; Annunziata, S.; Ciccimarra, F.; Rubino, A. Reactive nitrogen species modulate the effects of rhein, an active component of senna laxatives, on human epithelium in vitro. J. Pediatr. Gastroenterol. Nutr., 2002, 34(5), 529-534.
[http://dx.doi.org/10.1097/00005176-200205000-00011] [PMID: 12050580]
[20]
Nie, C.; Zhang, F.; Ma, X.; Guo, R.; Zhou, S.; Zhao, L.; Xu, H.; Xiao, X.; Wang, Z. Determination of quality markers of Xuezhiling tablet for hyperlipidemia treatment. Phytomedicine, 2018, 44, 231-238.
[http://dx.doi.org/10.1016/j.phymed.2018.03.004] [PMID: 29631806]
[21]
Li, S.; Li, Q.; Lv, X.; Liao, L.; Yang, W.; Li, S.; Lu, P.; Zhu, D. Aurantio-obtusin relaxes systemic arteries through endothelial PI3K/AKT/eNOS-dependent signaling pathway in rats. J. Pharmacol. Sci., 2015, 128(3), 108-115.
[http://dx.doi.org/10.1016/j.jphs.2015.05.006] [PMID: 26076958]
[22]
Hou, J.; Gu, Y.; Zhao, S.; Huo, M.; Wang, S.; Zhang, Y.; Qiao, Y.; Li, X. Anti-inflammatory effects of Aurantio-Obtusin from seed of Cassia obtusifolia L. through modulation of the NF-κB pathway. Molecules, 2018, 23(12), 3093.
[http://dx.doi.org/10.3390/molecules23123093] [PMID: 30486383]
[23]
Kwon, K.S.; Lee, J.H.; So, K.S.; Park, B.K.; Lim, H.; Choi, J.S.; Kim, H.P. Aurantio-obtusin, an anthraquinone from cassiae semen, ameliorates lung inflammatory responses. Phytother. Res., 2018, 32(8), 1537-1545.
[http://dx.doi.org/10.1002/ptr.6082] [PMID: 29675883]
[24]
Vishnuprasad, C.N.; Tsuchiya, T.; Kanegasaki, S.; Kim, J.H.; Han, S.S. Aurantio-obtusin stimulates chemotactic migration and differentiation of MC3T3-E1 osteoblast cells. Planta Med., 2014, 80(7), 544-549.
[http://dx.doi.org/10.1055/s-0034-1368445] [PMID: 24841966]
[25]
Wojcikowski, K.; Johnson, D.W.; Gobe, G. Herbs or natural substances as complementary therapies for chronic kidney disease: ideas for future studies. J. Lab. Clin. Med., 2006, 147(4), 160-166.
[http://dx.doi.org/10.1016/j.lab.2005.11.011] [PMID: 16581343]
[26]
Fang, F.; Wang, J.B.; Zhao, Y.L.; Jin, C.; Kong, W.J.; Zhao, H.P.; Wang, H.J.; Xiao, X.H. A comparative study on the tissue distributions of rhubarb anthraquinones in normal and CCl4-injured rats orally administered rhubarb extract. J. Ethnopharmacol., 2011, 137(3), 1492-1497.
[http://dx.doi.org/10.1016/j.jep.2011.08.028] [PMID: 21884773]
[27]
Zhu, W.; Wang, X.M.; Zhang, L.; Li, X.Y.; Wang, B.X. Pharmacokinetic of rhein in healthy male volunteers following oral and retention enema administration of rhubarb extract: a single dose study. Am. J. Chin. Med., 2005, 33(6), 839-850.
[http://dx.doi.org/10.1142/S0192415X05003508] [PMID: 16355440]
[28]
Jiang, J.Y.; Yang, M.W.; Qian, W.; Lin, H.; Geng, Y.; Zhou, Z.Q.; Xiao, D.W. Quantitative determination of rhein in human plasma by liquid chromatography-negative electrospray ionization tandem mass/mass spectrometry and the application in a pharmacokinetic study. J. Pharm. Biomed. Anal., 2012, 57, 19-25.
[http://dx.doi.org/10.1016/j.jpba.2011.09.001] [PMID: 21945452]
[29]
Sun, H.; Luo, G.; Xiang, Z.; Cai, X.; Chen, D. Pharmacokinetics and pharmacodynamics study of rhein treating renal fibrosis based on metabonomics approach. Phytomedicine, 2016, 23(13), 1661-1670.
[http://dx.doi.org/10.1016/j.phymed.2016.10.002] [PMID: 27823631]
[30]
Takizawa, Y.; Morota, T.; Takeda, S.; Aburada, M. Pharmacokinetics of rhein from Onpi-to, an oriental herbal medicine, in rats. Biol. Pharm. Bull., 2003, 26(5), 613-617.
[http://dx.doi.org/10.1248/bpb.26.613] [PMID: 12736499]
[31]
Tang, W.F.; Huang, X.; Yu, Q.; Qin, F.; Wan, M.H.; Wang, Y.G.; Liang, M.Z. Determination and pharmacokinetic comparison of rhein in rats after oral dosed with Da-Cheng-Qi decoction and Xiao-Cheng-Qi decoction. Biomed. Chromatogr., 2007, 21(11), 1186-1190.
[http://dx.doi.org/10.1002/bmc.873] [PMID: 17582236]
[32]
Gong, H.; Tang, W.; Wang, H.; Xia, Q.; Huang, X. Effects of food and gender on the pharmacokinetics of rhein and emodin in rats after oral dosing with Da-Cheng-Qi decoction. Phytother. Res., 2011, 25(1), 74-80.
[http://dx.doi.org/10.1002/ptr.3223] [PMID: 20623608]
[33]
Zhang, Y.X.; Li, J.S.; Peng, W.W.; Liu, X.; Yang, G.M.; Chen, L.H.; Cai, B.C. Comparative pharmacokinetics of aloe-emodin, rhein and emodin determined by liquid chromatography-mass spectrometry after oral administration of a rhubarb peony decoction and rhubarb extract to rats. Pharmazie, 2013, 68(5), 333-339.
[PMID: 23802430]
[34]
Qin, F.; Huang, J.; Huang, X.; Ren, P. Simultaneous determination and pharmacokinetic comparisons of aloe-emodin, rhein, emodin, and chrysophanol after oral administration of these monomers, Rhei Rhizoma and Chaiqin-Chengqi-Tang, to rats. J. Liq. Chromatogr. Relat. Technol., 2011, 34(14), 1381-1390.
[http://dx.doi.org/10.1080/10826076.2011.572211]
[35]
Huang, P.; Gao, J.W.; Shi, Z.; Zou, J.L.; Lu, Y.S.; Yuan, Y.M.; Yao, M.C. A novel UPLC-MS/MS method for simultaneous quantification of rhein, emodin, berberine and baicalin in rat plasma and its application in a pharmacokinetic study. Bioanalysis, 2012, 4(10), 1205-1213.
[http://dx.doi.org/10.4155/bio.12.81] [PMID: 22651564]
[36]
Hou, M.L.; Chang, L.W.; Lin, C.H.; Lin, L.C.; Tsai, T.H. Determination of bioactive components in Chinese herbal formulae and pharmacokinetics of rhein in rats by UPLC-MS/MS. Molecules, 2014, 19(4), 4058-4075.
[http://dx.doi.org/10.3390/molecules19044058] [PMID: 24699148]
[37]
Mai, X.; Zhang, Y.; Ma, H.; Xu, Z.; Yang, Y.; Wang, H.; Ouyang, L.; Liu, S. Comparative pharmacokinetics and metabolic profile of Rhein following oral administration of Niuhuang Shang Qing tablets, Rhubarb and Rhein in rats. Int. J. Pharmacol., 2019, 15(1), 19-30.
[http://dx.doi.org/10.3923/ijp.2019.19.30]
[38]
Hou, M.L.; Chang, L.W.; Lin, C.H.; Lin, L.C.; Tsai, T.H. Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes. J. Ethnopharmacol., 2014, 155(2), 1291-1299.
[http://dx.doi.org/10.1016/j.jep.2014.07.022] [PMID: 25046826]
[39]
Zhang, A.; Sun, H.; Wang, X.; Jiao, G.; Yuan, Y.; Sun, W. Simultaneous in vivo RP-HPLC-DAD quantification of multiple-component and drug-drug interaction by pharmacokinetics, using 6,7-dimethylesculetin, geniposide and rhein as examples. Biomed. Chromatogr., 2012, 26(7), 844-850.
[http://dx.doi.org/10.1002/bmc.1739] [PMID: 22068685]
[40]
Hsueh, T.P.; Tsai, T.H. Preclinical pharmacokinetics of Scoparone, Geniposide and Rhein in an herbal medicine using a validated LC-MS/MS method. Molecules, 2018, 23(10), 2716.
[http://dx.doi.org/10.3390/molecules23102716] [PMID: 30360359]
[41]
Cong, X.D.; Fu, P.R.; Dai, D.Z.; Zhang, Y.; Dai, Y. Pharmacokinetic behavior of argirein, derived from rhein, is characterized as slow release and prolonged T1/2 of rhein in rats. Eur. J. Pharm. Sci., 2012, 46(5), 468-474.
[http://dx.doi.org/10.1016/j.ejps.2012.03.014] [PMID: 22521276]
[42]
Luo, J.; Sun, J.; Luo, X.; Wei, Y.; Zheng, H.; Mu, C.; Yao, W. Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery: synthesis, characterization, and pharmacokinetics. Drug Dev. Ind. Pharm., 2019, 45(1), 96-104.
[http://dx.doi.org/10.1080/03639045.2018.1522326] [PMID: 30196732]
[43]
Wei, Y.; Luo, X.; Guan, J.; Ma, J.; Zhong, Y.; Luo, J.; Li, F. Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics. Drug Dev. Ind. Pharm., 2017, 43(11), 1885-1891.
[http://dx.doi.org/10.1080/03639045.2017.1353519] [PMID: 28692315]
[44]
Dai, X.Y.; Yan, Y.L.; Wu, Q.F.; Yu, C.H.; Liu, X.; Jiang, Y.Q. Comparative pharmacokinetics of rhein and chrysophanol after oral administration of Quyu Qingre granules in normal and acute blood stasis rabbits. J. Ethnopharmacol., 2014, 153(2), 338-343.
[http://dx.doi.org/10.1016/j.jep.2014.02.005] [PMID: 24642020]
[45]
Lang, W. Pharmacokinetics of 14C-labelled rhein in rats. Pharmacology, 1988, 36(1)(Suppl. 1), 158-171.
[http://dx.doi.org/10.1159/000138436] [PMID: 3368515]
[46]
Dahms, M.; Lotz, R.; Lang, W.; Renner, U.; Bayer, E.; Spahn-Langguth, H. Elucidation of phase I and phase II metabolic pathways of rhein: species differences and their potential relevance. Drug Metab. Dispos., 1997, 25(4), 442-452.
[PMID: 9107544]
[47]
Song, R.; Xu, L.; Xu, F.; Dong, H.; Tian, Y.; Zhang, Z. Metabolic analysis of rhubarb extract by rat intestinal bacteria using liquid chromatography-tandem mass spectrometry. Biomed. Chromatogr., 2011, 25(3), 417-426.
[http://dx.doi.org/10.1002/bmc.1467] [PMID: 21321975]
[48]
Zhu, H.; Bi, K.; Han, F.; Guan, J.; Zhang, X.; Mao, X.; Zhao, L.; Li, Q.; Hou, X.; Yin, R. Identification of the absorbed components and metabolites of Zhi-Zi-Da-Huang decoction in rat plasma by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. J. Pharm. Biomed. Anal., 2015, 111, 277-287.
[http://dx.doi.org/10.1016/j.jpba.2015.03.043] [PMID: 25912849]
[49]
Ma, H.; Liu, Y.; Mai, X.; Liao, Y.; Zhang, K.; Liu, B.; Xie, X.; Du, Q. Identification of the constituents and metabolites in rat plasma after oral administration of HuanglianShangqing pills by ultra high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J. Pharm. Biomed. Anal., 2016, 125, 194-204.
[http://dx.doi.org/10.1016/j.jpba.2016.03.038] [PMID: 27031575]
[50]
Xu, Y.; Mao, X.; Qin, B.; Peng, Y.; Zheng, J. In vitro and in vivo metabolic activation of rhein and characterization of glutathione conjugates derived from rhein. Chem. Biol. Interact., 2018, 283, 1-9.
[http://dx.doi.org/10.1016/j.cbi.2018.01.001] [PMID: 29331654]
[51]
Lee, J.H.; Kim, J.M.; Kim, C. Pharmacokinetic analysis of rhein in Rheum undulatum L. J. Ethnopharmacol., 2003, 84(1), 5-9.
[http://dx.doi.org/10.1016/S0378-8741(02)00222-2] [PMID: 12499069]
[52]
Sun, H.; Yin, Q.; Zhang, A.; Wang, X. UPLC-MS/MS performing pharmacokinetic and biodistribution studies of rhein. J. Sep. Sci., 2012, 35(16), 2063-2068.
[http://dx.doi.org/10.1002/jssc.201200378] [PMID: 22753114]
[53]
Sund, R.B.; Elvegård, S.O. Anthraquinone laxatives: metabolism and transport of danthron and rhein in the rat small and large intestine in vitro. Pharmacology, 1988, 36(1)(Suppl. 1), 144-151.
[http://dx.doi.org/10.1159/000138434] [PMID: 3368513]
[54]
de Witte, P.; Van Hoestenberghe, A.; Eyssen, H. In vitro reduction of rhein anthraquinone to rhein anthrone by rat cecal microflora and some intestinal bacterial strains. Biopharm. Drug Dispos., 1992, 13(4), 243-253.
[http://dx.doi.org/10.1002/bdd.2510130403] [PMID: 1600110]
[55]
Tang, J.C.; Yang, H.; Song, X.Y.; Song, X.H.; Yan, S.L.; Shao, J.Q.; Zhang, T.L.; Zhang, J.N. Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother. Res., 2009, 23(2), 159-164.
[http://dx.doi.org/10.1002/ptr.2572] [PMID: 18814214]
[56]
He, L.N.; Yang, A.H.; Cui, T.Y.; Zhai, Y.R.; Zhang, F.L.; Chen, J.X.; Jin, C.H.; Fan, Y.W.; Wu, Z.J.; Wang, L.L.; He, X. Reactive metabolite activation by CYP2C19-mediated rhein hepatotoxicity. Xenobiotica, 2015, 45(4), 361-372.
[http://dx.doi.org/10.3109/00498254.2014.984794] [PMID: 25815638]
[57]
Wu, W.; Hu, N.; Zhang, Q.; Li, Y.; Li, P.; Yan, R.; Wang, Y. In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver microsomes from humans and rats. Chem. Biol. Interact., 2014, 219, 18-27.
[http://dx.doi.org/10.1016/j.cbi.2014.05.006] [PMID: 24854283]
[58]
Yuan, Y.; Zheng, J.; Wang, M.; Li, Y.; Ruan, J.; Zhang, H. Metabolic activation of rhein: insights into the potential toxicity induced by rhein-containing herbs. J. Agric. Food Chem., 2016, 64(28), 5742-5750.
[http://dx.doi.org/10.1021/acs.jafc.6b01872] [PMID: 27362917]
[59]
Dai, Y.C.; Deng, N.; Liu, W. Study on pharmacokinetics of aurantio-obtusin in normal rats. Zhongguo Yiyuan Yaoxue Zazhi, 2015, 35(14), 1271-1274.
[60]
Zhang, N.; Dong, N.; Pang, L.; Xu, H.; Ji, H. Quantitative determination and pharmacokinetic study of aurantio-obtusin in rat plasma by liquid chromatography-mass spectrometry. J. Chromatogr. Sci., 2014, 52(9), 1059-1064.
[http://dx.doi.org/10.1093/chromsci/bmt159] [PMID: 24149003]
[61]
Yang, C.; Wang, S.; Guo, X.; Sun, J.; Liu, L.; Wu, L. Simultaneous determination of seven anthraquinones in rat plasma by Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry and pharmacokinetic study after oral administration of Semen Cassiae extract. J. Ethnopharmacol., 2015, 169, 305-313.
[http://dx.doi.org/10.1016/j.jep.2015.04.008] [PMID: 25907980]
[62]
Guo, R.; Wu, H.; Yu, X.; Xu, M.; Zhang, X.; Tang, L.; Wang, Z. Simultaneous determination of seven anthraquinone aglycones of crude and processed Semen Cassiae extracts in rat plasma by UPLC-MS/MS and its application to a comparative pharmacokinetic study. Molecules, 2017, 22(11), 1083-1096.
[http://dx.doi.org/10.3390/molecules22111803] [PMID: 29143757]
[63]
Yang, B.; Xie, L.; Peng, S.; Sun, K.; Jin, J.; Zhen, Y.; Qin, K.; Cai, B. Nine components pharmacokinetic study of rat plasma after oral administration raw and prepared Semen Cassiae in normal and acute liver injury rats. J. Sep. Sci., 2019, 42(14), 2341-2350.
[http://dx.doi.org/10.1002/jssc.201900007] [PMID: 31037812]
[64]
Xie, L.; Liu, X.; Zhu, X.; Xu, Y.; Peng, S.; Sun, K.; Cai, H.; Dai, Q.; Wang, C.; Zhou, Q.; Cai, B. Development of an UHPLC-MS/MS method for comparative pharmacokinetics of nine anthraquinones in rats and application to dosage conversion between different Semen Cassiae forms. J. Pharm. Biomed. Anal., 2019, 174, 696-706.
[http://dx.doi.org/10.1016/j.jpba.2019.07.001] [PMID: 31288192]
[65]
Xu, L.L. Effect of Semen Cassiae on CY450 Enzymes and Related Metabolomics in Rat Liver Master thesis: Anhui Medical University: Hefei, 2017.
[66]
Mi, B.L.; Sun, Q.; Qu, Y.Q.; Gao, X.X.; Yu, Z.W.; Ge, G.B.; Cai, S.S.; Zhang, J.; Zheng, Y.C.; Zhang, Z.Q. Glucuronidation of aurantio-obtusin: identification of human UDP-glucuronosyltransferases and species differences. Xenobiotica, 2014, 44(8), 716-721.
[http://dx.doi.org/10.3109/00498254.2014.895881] [PMID: 24618000]

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